Project Summary Recent advances in pharmacological treatment for cognitive deficits in fragile X syndrome (FXS) and Down Syndrome (DS) have been numerous, resulting in a number of clinical trials that will soon proceed to stages of human testing in children and adults. However, treatment studies in individuals with intellectual disabilities (ID) face a number of measurement challenges, and few studies have been conducted to assess the suitability of neuropsychological measures for use in children with ID. In particular, while several pharmacological agents target the function of the hippocampus and associated memory systems, relatively little work has been completed to validate measures assessing function in this domain. Given that a number of proposed pharmacological agents target the function of the hippocampus, memory will likely be designated as a ?primary? outcome in a number of upcoming trials. This makes memory test validation a critical next step in supporting pharmacological approaches to cognitive interventions in ID. Thus, in the current proposal we plan to further develop and validate a theoretically-informed, comprehensive android touch-screen memory assessment system for use in young children with ID. Across 3 sites (University of Arizona, UC Davis, Drexel University) with extensive expertise in research with ID groups, we will first establish the usability, internal consistency, and form equivalence of the measure in 30 typically developing 3 year olds (Phase 1). In Phase 2, we will test the properties in a group with DS or FXS (n = 30, age 6H18 years) after measure revision and input from consultants and PIs. In Phase 3, we will determine the psychometric properties of the memory assessment in 180 children with DS and FXS (n=90 per group). We will evaluate floor and ceiling effects, internal consistency, validity, and sensitivity to developmental change and ID group effects. To determine the validity of each measure, we will correlate each test with other assessments, including the NIH Toolbox Early Childhood Battery, IQ, adaptive behavior, and parent-reported memory. Comparisons with mental age matched controls (n = 90, ages 3 to 6 years) will determine the sensitivity of the measures to detect group differences and cross-sectional age-related change during a critical period of memory development. The DS and FXS children will be re-assessed at 4 and 24 weeks to assess measurement retest- reliability and stability. As effective measures are required across a wide age range and in individuals with differing background characteristics, we will test how each measure?s psychometric properties may vary based on age and participant?s level of attention. We hope to better understand which subject characteristics might lead to inconsistent performance and define which measures may be effective across the majority of children with these syndromes. Through this work, we will provide evidence to help determine which measures may be strong primary outcomes for clinical trials in DS and FXS. The results of this investigation will provide a methodological advance that will set the field forward toward more consistent and valid assessment of this important domain for intervention studies of drug therapies as well as in behavioral cognitive interventions.